Characteristics of drug-resistant tuberculosis in Abkhazia (Georgia), a high-prevalence area in Eastern Europe

Although multidrug-resistant (MDR) tuberculosis (TB) is a major public health problem in Eastern Europe, the factors contributing to emergence, spread and containment of MDR-TB are not well defined. Here, we analysed the characteristics of drug-resistant TB in a cross-sectional study in Abkhazia (Georgia) between 2003 and 2005, where standard short-course chemotherapy is supplemented with individualized drug-resistance therapy. Drug susceptibility testing (DST) and molecular typing were carried out for Mycobacterium tuberculosis complex strains from consecutive smear-positive TB patients. Out of 366 patients, 60.4% were resistant to any first-line drugs and 21% had MDR-TB. Overall, 25% of all strains belong to the Beijing genotype, which was found to be strongly associated with the risk of MDR-TB (OR 25.9, 95% CI 10.2-66.0) and transmission (OR 2.8, 95% CI 1.6-5.0). One dominant MDR Beijing clone represents 23% of all MDR-TB cases. The level of MDR-TB did not decline during the study period, coinciding with increasing levels of MDR Beijing strains among previously treated cases. Standard chemotherapy plus individualized drug-resistance therapy, guided by conventional DST, might be not sufficient to control MDR-TB in Eastern Europe in light of the spread of "highly transmissible" MDR Beijing strains circulating in the community

Treatment of tuberculosis in a region with high drug resistance: Outcomes, drug resistance amplification and re-infection

Introduction: Emerging antituberculosis drug resistance is a serious threat for tuberculosis (TB) control, especially in Eastern European countries. Methods: We combined drug susceptibility results and molecular strain typing data with treatment outcome reports to assess the influence of drug resistance on TB treatment outcomes in a prospective cohort of patients from Abkhazia (Georgia). Patients received individualized treatment regimens based on drug susceptibility testing (DST) results. Definitions for antituberculosis drug resistance and treatment outcomes were in line with current WHO recommendations. First and second line DST, and molecular typing were performed in a supranational laboratory for Mycobacterium tuberculosis (MTB) strains from consecutive sputum smear-positive TB patients at baseline and during treatment. Results: At baseline, MTB strains were fully drug-susceptible in 189/326 (58.0%) of patients. Resistance to at least H or R (PDR-TB) and multidrug-resistance (MDR-TB) were found in 69/326 (21.2%) and 68/326 (20.9%) of strains, respectively. Three MDR-TB strains were also extensively resistant (XDR-TB). During treatment, 3/189 (1.6%) fully susceptible patients at baseline were re-infected with a MDR-TB strain and 2/58 (3.4%) PDR-TB patients became MDR-TB due to resistance amplification. 5/ 47 (10.6%) MDR- patients became XDR-TB during treatment. Treatment success was observed in 161/189 (85.2%), 54/69 (78.3%) and 22/68 (32.3%) of patients with fully drug susceptible, PDR- and MDR-TB, respectively. Development of ofloxacin resistance was significantly associated with a negative treatment outcome. Conclusion: In Abkhazia, a region with high prevalence of drug resistant TB, the use of individualized MDR-TB treatment regimens resulted in poor treatment outcomes and XDR-TB amplification. Nosocomial transmission of MDR-TB emphasizes the importance of infection control in hospitals

Stain-Free Quantification of Chromosomes in Live Cells Using Regularized Tomographic Phase Microscopy

Refractive index imaging is a label-free technique that enables long-term monitoring of the internal structures and molecular composition in living cells with minimal perturbation. Existing tomographic methods for the refractive index imaging lack 3-D resolution and result in artifacts that prevent accurate refractive index quantification. To overcome these limitations without compromising the capability to observe a sample in its most native condition, we have developed a regularized tomographic phase microscope (RTPM) enabling accurate refractive index imaging of organelles inside intact cells. With the enhanced accuracy, we quantify the mass of chromosomes in intact living cells, and differentiate two human colon cancer lines, HT-29 and T84 cells, solely based on the non-aqueous (dry) mass of chromosomes. In addition, we demonstrate chromosomal imaging using a dual-wavelength RTPM, which shows its potential to determine the molecular composition of cellular organelles in live cells.National Institute of Biomedical Imaging and Bioengineering (U.S.) (9P41EB015871-26A1

Strategies to overcome physician shortages in northern Ontario: A study of policy implementation over 35 years

<p>Abstract</p> <p>Background</p> <p>Shortages and maldistibution of physicians in northern Ontario, Canada, have been a long-standing issue. This study seeks to document, in a chronological manner, the introduction of programmes intended to help solve the problem by the provincial government over a 35-year period and to examine several aspects of policy implementation, using these programmes as a case study.</p> <p>Methods</p> <p>A programme analysis approach was adopted to examine each of a broad range of programmes to determine its year of introduction, strategic category, complexity, time frame, and expected outcome. A chronology of programme initiation was constructed, on the basis of which an analysis was done to examine changes in strategies used by the provincial government from 1969 to 2004.</p> <p>Results</p> <p>Many programmes were introduced during the study period, which could be grouped into nine strategic categories. The range of policy instruments used became broader in later years. But conspicuous by their absence were programmes of a directive nature. Programmes introduced in more recent years tended to be more complex and were more likely to have a longer time perspective and pay more attention to physician retention. The study also discusses the choice of policy instruments and use of multiple strategies.</p> <p>Conclusion</p> <p>The findings suggest that an examination of a policy is incomplete if implementation has not been taken into consideration. The study has revealed a process of trial-and-error experimentation and an accumulation of past experience. The study sheds light on the intricate relationships between policy, policy implementation and use of policy instruments and programmes.</p

Mutations in two global regulators lower individual mortality in Escherichia coli

There has been considerable investigation into the survival of bacterial cells under stress conditions, but little is known about the causes of mortality in the absence of exogenous stress. That there is a basal frequency of cell death in such populations may reflect that it is either impossible to avoid all lethal events, or alternatively, that it is too costly. Here, through a genetic screen in the model organism Escherichia coli, we identify two mutants with lower frequencies of mortality: rssB and fliA. Intriguingly, these two genes both affect the levels of different sigma factors within the cell. The rssB mutant displays enhanced resistance to multiple external stresses, possibly indicating that the cell gains its increased vitality through elevated resistance to spontaneous, endogenous stresses. The loss of fliA does not result in elevated stress resistance; rather, its survival is apparently due to a decreased physical stress linked to the insertion of the flagellum through the membrane and energy saved through the loss of the motor proteins. The identification of these two mutants implies that reducing mortality is not impossible; rather, due to its cost, it is subject to trade-offs with other traits that contribute to the competitive success of the organism

The role of wages in the migration of health care professionals from developing countries

Several countries are increasingly relying on immigration as a means of coping with domestic shortages of health care professionals. This trend has led to concerns that in many of the source countries – especially within Africa – the outflow of health care professionals is adversely affecting the health care system. This paper examines the role of wages in the migration decision and discusses the likely effect of wage increases in source countries in slowing migration flows. This paper uses data on wage differentials in the health care sector between source country and receiving country (adjusted for purchasing power parity) to test the hypothesis that larger wage differentials lead to a larger supply of health care migrants. Differences in other important factors affecting migration are discussed and, where available, data are presented. There is little correlation between the supply of health care migrants and the size of the wage differential between source and destination country. In cases where data are available on other factors affecting migration, controlling for these factors does not affect the result. At current levels, wage differentials between source and destination country are so large that small increases in health care wages in source countries are unlikely to affect significantly the supply of health care migrants. The results suggest that non-wage instruments might be more effective in altering migration flows

Phenotypic Variation and Bistable Switching in Bacteria

Microbial research generally focuses on clonal populations. However, bacterial cells with identical genotypes frequently display different phenotypes under identical conditions. This microbial cell individuality is receiving increasing attention in the literature because of its impact on cellular differentiation, survival under selective conditions, and the interaction of pathogens with their hosts. It is becoming clear that stochasticity in gene expression in conjunction with the architecture of the gene network that underlies the cellular processes can generate phenotypic variation. An important regulatory mechanism is the so-called positive feedback, in which a system reinforces its own response, for instance by stimulating the production of an activator. Bistability is an interesting and relevant phenomenon, in which two distinct subpopulations of cells showing discrete levels of gene expression coexist in a single culture. In this chapter, we address techniques and approaches used to establish phenotypic variation, and relate three well-characterized examples of bistability to the molecular mechanisms that govern these processes, with a focus on positive feedback.

Analysis of vaginal microbicide film hydration kinetics by quantitative imaging refractometry

We have developed a quantitative imaging refractometry technique, based on holographic phase microscopy, as a tool for investigating microscopic structural changes in water-soluble polymeric materials. Here we apply the approach to analyze the structural degradation of vaginal topical microbicide films due to water uptake. We implemented transmission imaging of 1-mm diameter film samples loaded into a flow chamber with a 1.5×2 mm field of view. After water was flooded into the chamber, interference images were captured and analyzed to obtain high resolution maps of the local refractive index and subsequently the volume fraction and mass density of film material at each spatial location. Here, we compare the hydration dynamics of a panel of films with varying thicknesses and polymer compositions, demonstrating that quantitative imaging refractometry can be an effective tool for evaluating and characterizing the performance of candidate microbicide film designs for anti-HIV drug delivery. © 2014 Rinehart et al

Do nasogastric tubes worsen dysphagia in patients with acute stroke?

<p>Abstract</p> <p>Background</p> <p>Early feeding via a nasogastric tube (NGT) is recommended as safe way of supplying nutrition in patients with acute dysphagic stroke. However, preliminary evidence suggests that NGTs themselves may interfere with swallowing physiology. In the present study we therefore investigated the impact of NGTs on swallowing function in acute stroke patients.</p> <p>Methods</p> <p>In the first part of the study the incidence and consequences of pharyngeal misplacement of NGTs were examined in 100 stroke patients by fiberoptic endoscopic evaluation of swallowing (FEES). In the second part, the effect of correctly placed NGTs on swallowing function was evaluated by serially examining 25 individual patients with and without a NGT in place.</p> <p>Results</p> <p>A correctly placed NGT did not cause a worsening of stroke-related dysphagia. Except for two cases, in which swallowing material got stuck to the NGT and penetrated into the laryngeal vestibule after the swallow, no changes of the amount of penetration and aspiration were noted with the NGT in place as compared to the no-tube condition. Pharyngeal misplacement of the NGT was identified in 5 of 100 patients. All these patients showed worsening of dysphagia caused by the malpositioned NGT with an increase of pre-, intra-, and postdeglutitive penetration.</p> <p>Conclusion</p> <p>Based on these findings, there are no principle obstacles to start limited and supervised oral feeding in stroke patients with a NGT in place.</p

Provider payments and patient charges as policy tools for cost-containment: How successful are they in high-income countries?

In this paper, we focus on those policy instruments with monetary incentives that are used to contain public health expenditure in high-income countries. First, a schematic view of the main cost-containment methods and the variables in the health system they intend to influence is presented. Two types of instruments to control the level and growth of public health expenditure are considered: (i) provider payment methods that influence the price and quantity of health care, and (ii) cost-containment measures that influence the behaviour of patients. Belonging to the first type of instruments, we have: fee-for-service, per diem payment, case payment, capitation, salaries and budgets. The second type of instruments consists of patient charges and reference price systems for pharmaceuticals. Secondly, we provide an overview of experience in high-income countries that use or have used these particular instruments. Finally, the paper assesses the overall potential of these instruments in cost-containment policies